PXD026941-1

PXD026941 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of the role of the quality control protease LONP1 in mitochondrial protein aggregation
Description	The mitochondrial matrix protease LONP1 is an essential part of the organellar protein quality control system. LONP1 has been shown to be involved in respiration control and apoptosis. Furthermore, a reduction in LONP1 level correlates with ageing processes. Up to now, the effects of a LONP1 defect were mostly studied by utilizing transient, siRNA-mediated knockdown approaches. We generated a new cellular model system for studying the impact of LONP1 on mitochondrial protein homeostasis by a CRISPR/Cas-mediated genetic knockdown (gKD). These cells show a stable reduction of LONP1 along with a mild phenotype characterized by absent morphological differences and only small negative effects on mitochondrial functions under normal culture conditions. To assess the consequences of a permanent LONP1 depletion on the mitochondrial proteome, we analyzed the alterations of protein levels by quantitative mass spectrometry, demonstrating small adaptive changes, in particular concerning mitochondrial protein biogenesis. In an additional proteomic analysis, we determined the temperature-dependent aggregation behavior of mitochondrial proteins and its dependence on a reduction of LONP1 activity, demonstrating the important role of the protease for mitochondrial protein homeostasis in mammalian cells. We identified a significant number of mitochondrial proteins that are affected by LONP1 activity concerning their stressinduced solubility. Taken together, our results suggest a very good applicability of the LONP1 gKD cell line as a model system for human ageing processes.
HostingRepository	PRIDE
AnnounceDate	2022-01-31
AnnouncementXML	Submission_2022-01-31_08:06:23.681.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026941
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marc Sylvester
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine; 6x(13)C labeled residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-27 15:30:08	ID requested
⏵ 1	2022-01-31 08:06:24	announced

Pollecker K, Sylvester M, Voos W, Proteomic analysis demonstrates the role of the quality control protease LONP1 in mitochondrial protein aggregation. J Biol Chem, 297(4):101134(2021) [pubmed]

submitter keyword: Human, mitochondria, Genetic alteration via Crispr/CAS, Protein degradation, Protein aggregation, Heat stress, LONP1 ATP-dependent protease

Wolfgang Voos
contact affiliation	University of Bonn, Germany
contact email	wolfgang.voos@uni-bonn.de
lab head
Marc Sylvester
contact affiliation	Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn
contact email	msylvest@uni-bonn.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026941
     1. Label: PRIDE project
     2. Name: Proteomic analysis of the role of the quality control protease LONP1 in mitochondrial protein aggregation